Surface plasmon resonance (SPR) is a universal tool for studying and characterizing macromolecular interaction in a label-free state. The system detects the binding reaction in real time by monitoring changes in mass concentration at the chip surface;the association and dissociation rate constants are determined directly from the reaction traces. Samples ranging from small molecules to crude extracts, lipid vesicles, viruses, bacteria and eukaryotic cells can be studied in real-time, without the use of labels and with little or no prior sample preparation. Funding is requested for the state-of-the-art SPR biosensor, Biacore T100 to replace a 16 year old Biacore 1000 instrument. The requested instrument and service will replace the old system and will be located in a core facility, the Biophysics Resource of Keck Laboratory, and will be available to anyone needing application of SPR in his or her research. The Deputy Dean of Yale School of Medicine has committed $60,000 for the purchase of a service contract for maintenance of the requested T100 system, which will largely ensure the smooth operation of the instrument for at least 4 years. There is currently no comparable instrument on the campus of Yale School of Medicine;thus the new instrument will significantly enhance the local SPR capabilities. The research needs of the research projects that will utilize the requested SPR instrument have exceeded the capabilities of the old SPR system available as an "open access" instrument in the core facility setting. These needs include: serially addressed cells that allow referencing in real time, better sensitivity to detect interactions with molecules of low molecular weight (<1000 Da), buffer switching capabilities, and higher throughput for screening interactions with drug libraries. The requested Biacore T100 system is versatile and would support 14 NIH-funded projects directed by 15 investigators from Yale School of Medicine. These investigators propose to use the SPR technology to advance diverse biomedical research on: immune response, drug abuse, Salmonellosis (which continues to be a major world-wide health concern and has an estimated annual economic impact on the U.S. of $3 billion), prolactin receptor, a potassium channel protein involved in acquired long QT syndrome, a life-threatening heart syndrome, design of vaccines against HIV infection, discovery of broad-spectrum therapeutics that may be effective against multiple bacterial pathogens, and the development of drugs for protein targets that are associated with microbial infections, trauma, autoimmune diseases, and cancer. Progress in this research will likely advance our knowledge of how best to understand, prevent, and treat human diseases. The requested T100 system would be unique to Yale University, but it will be also open for use to any interested investigator due to its placement in a core facility that accepts samples from all over the world;thus, the requested T100 would surely make a significant contribution to biomedical research that would extend beyond Yale University.